Peripheral Blood Of Children Research Articles

The changes and clinical significance of CD62P、 PAIgG、 Tr cell in children with acute idiopathic thrombocytopenic purpura pateints

Objective To analyze the changes of PAIgG, CD62P, CD4+CD25+ Foxp3+Tr,and IL-18 before and after treatment in peripheral blood of children with acute idiopathic thrombocytopenic purpura(ITP) and investigate the function of these factors in the pathogenesis of ITP.Methods Forty-one cases of acute ITP children were divided into the effective group(35cases) and the ineffective group (6cases) according to the clinical treatment. To detect PAIgG,CD62P,and the number of Tr cells by using flow cytometry ,IL-18 plasma levels by ELISA assay,and analyze the variations of these indicators before and after treatment in children with acute ITP. Results In the effective treatment group, PAIgG, CD62P before treatment were 53.05%,(14.18±5.04 )%, which were significantly higher than that after treatment [18.62%, ( 8.36±1.95 )%] and control group[5.26%,(2.65±0.59) %,all P<0.01],and PAIgG,CD62P after treatment were also higher than that in control group [all P<0.05].IL-18,CD4 + T lymphocytes, Tr/CD4+T-lymphocyte ratios before treatment [415.47 ±38.92 ) ng/L,( 25.64 ± 5.81 )%,( 2.67 ± 0.14 )%]were significantly lower than that after treatment [(512.85±42. 17)ng/L,(35.08±6.07)% ,(4.76±0.58)%] and control group[(506. 39±32.28) ng/L,(35.32±2.27)% ,(5.37 ±0.69)% ,all P<0.01]. IL-18, CD4 +T lymphocytes, Tr/CD4 +T-lymphocyte ratios after treatmenthad no statistically significant difference compared with control group( all P<0.05 ). In ineffective group, the test results of PAIgG, CD62P, IL-18, CD4 +T lymphocytes, Tr/CD4+ T-lymphocyte ratios showed no significant change before and after treatment( all P<0.05 ).IL-18 had negative correlations with PAIgG,CD62P respectively before and after treatment(all P<0.05 ). Tr cells / CD4 + T had negative correlations with PAIgG,CD62P respectively (all P<0.05). Conclusions The amount of Tr, IL-18 were reduced, while CD62P and PAIgG increased in peripheral blood of children with acute ITP. IL-18, Tr , CD62P and PAIgG play important roles in the pathogenesis of acute ITP. Key words: Acute idiopathic thrombocytopenic purpura; Regulation T cells; Enzyme linked immunosorbent assay; Interleukin -18, Platelet associated IgG; CD62P

Evaluation of T regulatory cell apoptosis in children with newly recognized type 1 diabetes mellitus

BackgroundType 1 diabetes is a metabolic disease characterized by an autoimmune, T-cell dependent destruction of insulin producing pancreatic beta cells. T regulatory cells (Tregs) are critical regulators of immune tolerance.ObjectiveThe aim of the study was to investigate CD4+CD25highFoxP3 cell apoptosis in the peripheral blood of children with newly diagnosed type 1 diabetes mellitus.Methods34 children (15 girls and 19 boys) with new onset of type 1 diabetes mellitus, of the mean age 6.9 ± 5.2 (range 0.9-17.5 yr) and 18 healthy controls (8 girls, 10 boys) of the mean age 7.3 ± 4.6 (1.9-17.5 yr) were included into the study. Flow cytometric analysis of Tregs was performed using the following markers: anti-CD4, anti-CD25 and transcription factor FoxP3. Apoptosis was measured using anti-active caspase-3 monoclonal antibody. The percentage of apoptotic cells was measured within CD4+CD25highFoxP3+ cells.Results and conclusionThere was no statistically significant difference in the percentage of apoptotic CD4+CD25highFoxP3+ cells between children with diabetes and healthy subjects; the median value 0 (range 0-26.8) vs. 0 (range 0-2.6), respectively (P = 0.302). Further, clinical studies on a larger cohort of diabetic children are needed to evaluate T regulatory cell apoptosis, especially for future immune-based therapy.

Monitoring treatment response of childhood acute lymphocytic leukemia with certain molecular and biochemical markers

Apoptosis is the primary mechanism through which most chemotherapeutic agents induce tumor cell death. The purpose of this study was to monitor the expression of pro- and anti-apoptotic proteins CD(95) , Bcl-2, as well as copper and zinc levels in the peripheral blood of children with acute lymphocytic leukemia (ALL) prior to and 6 months after the beginning of chemotherapy. Blood parameters and bone marrow blast count were also assessed. Twenty of 26 patients who received treatment showed amelioration in apoptotic response, which is reflected in the elevation of CD(95) , whereas Bcl-2 protein was significantly lowered. In these patients, the elevated serum copper level was not significantly affected whereas the low serum zinc level was significantly raised. Improvement in blood parameters and bone marrow blast count were also achieved. Taken together, the data suggested that assessment of apoptosis signaling molecules might have a predictive impact on treatment outcome.

B cell subsets in healthy children: Reference values for evaluation of B cell maturation process in peripheral blood

The process of maturation of the immune system leads to generation of various lymphoid cell populations having the ability to react in specific way and expressing various markers on the cell surface. The study was set up to establish reference values for B lymphocyte subpopulations in peripheral blood of children and young adults to find the spectrum of their physiological age-related variation. Blood samples were taken from 292 children and young adults aged 0-31 years and tested for distribution of B cell subsets. Relative and absolute sizes of non-memory and memory, transitional, naïve, immature marginal zone-like/IgM-only memory, class-switched memory, double negative, activated, and plasmacytoid cell populations were determined by four-color flow cytometry, based on differential expression of CD19, IgM, IgD, CD21, CD27, and CD38. Significant variation both in relative, as well as in absolute numbers of individual cell populations in tested groups was observed. The reference values for age-related B cell subsets in eleven age groups, established as result of this study, may be used in diagnostics of any pathology related to B cell maturation process, as well as in attempts of correlating laboratory results with clinical symptoms of many defects affecting antibody production in pediatric population. Determination of B cell subpopulations carried in patients with antibody deficiencies may help to understand the nature of the disease and prevent its complications.

Mutation and expression of WNT8b gene and SHH gene in Hirschsprung disease

To investigate the relationship of WNT8b and SHH genes mutation and Hirschsprung disease(HSCR) in Chinese children. Preoperative whole blood preparations in 72 children with sporadic HSCR from northeast China were collected(study group). Seventy-two healthy children were used as controls(matched for sex and age). Genomic DNA was obtained from peripheral blood. Exon 1 of WNT8b gene and the exon 1 of SHH gene were analyzed for gene mutation. The mutation products were automatically sequenced. The levels of WNT8b and SHH mRNA were detected by quantitative real-time PCR(qRT-PCR) in blood samples. On sequencing, 13 out of 72 children with HSCR had WNT8b gene mutation in the coding area, including heterozygosity deletion in 8 cases (11.1%) and base replacement in 5(6.9%). Eleven children with HSCR had SHH gene mutation in the coding area including heterozygosity deletion in 7 cases(9.7%) and base replacement in 4(5.6%). No mutations in WNT8b and SHH genes were found in the control group. The WNT8b and SHH mRNA levels were different between the study group and the control group(30.01±1.13 vs. 17.33±0.62, and 28.25±1.27 vs. 18.94±0.31, P<0.05). WNT8b and SHH mutations and abnormal expressions are present in the peripheral blood of children with sporadic HSCR. These two genes may be related to the development of sporadic HSCR in children in the northeastern China.

Role of measuring the expression levels of a proliferation-inducing ligand and its receptors by real-time fluorescence quantitative method in children with lymphoma

to investigate the role of a real-time fluorescence quantitative polymerase chain reaction (PCR) in measuring the expression levels of a proliferation-inducing ligand and its receptors expression levels in peripheral blood of children with lymphoma. real-time fluorescence quantitative PCR was used to detect the expression levels of a proliferation-inducing ligand and its receptors in patients with Hodgkin disease (n = 10) or non-Hodgkin lymphoma (n = 37) and healthy control (n = 40). The correlation between the mRNA levels of a proliferation-inducing ligand and its receptors and differential stage of malignant lymphoma was analyzed. the results of 47 samples showed that the levels of proliferation-inducing ligand, B cell maturation antigen, transmembrane activator and CAML interactor in the peripheral blood of lymphoma in children were significantly higher than those in normal children (1.13 ± 0.09 vs 0.41 ± 0.09, 1.22 ± 0.11 vs 0.43 ± 0.10, 0.89 ± 0.12 vs 0.35 ± 0.08, all P < 0.05). The level of a proliferation-inducing ligand and its receptors had no significant difference between Hodgkin disease and non-Hodgkin lymphoma (P > 0.05). The level of a proliferation-inducing ligand in I-II stage (0.88 ± 0.06, 0.90 ± 0.08) of malignant lymphoma in children was significantly lower than that in III-IV stage (1.21 ± 0.09, 1.23 ± 0.09, P < 0.05) while the level of its receptors between various stages showed no difference (P > 0.05). the real-time fluorescence quantitative PCR has a high sensitivity and reproducibility. A proliferation-inducing ligand may play a great role in the development and progression of malignant lymphoma in children through its receptors of B cell maturation antigen, transmembrane activator and CAML interactor. A proliferation-inducing ligand and its receptors can be established as target molecules for early diagnosis and anti-cancer therapy.

Dendritic cell and T cell responses in children with food allergy

Food allergy (FA) and eosinophilic oesophagitis (EE) are increasingly common clinical problems. Dendritic cells (DCs) are key regulators of the sensitization and effector phases of allergic immune responses, but their role in these diseases is largely unknown. To evaluate for alterations in the phenotype and function of DCs in children with IgE-mediated milk allergy or EE compared with their non-affected siblings. Plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were prepared from peripheral blood of children with milk allergy (FA), EE, and non-affected siblings (CON). Purified pDCs and mDCs were cultured alone or with autologous CD4(+) lymphocytes. Cytokine levels in plasma, or culture supernatants following stimulation, were measured using multiplex array immunoassay. Cell-surface molecule expression was determined by flow cytometry. DCs from FA subjects produced greater levels of pro-inflammatory cytokines (IL-6, TNF-α), granulocyte macrophage-colony forming factor, and mDC-derived IL-10 compared with controls following allergen exposure. T(H) 2 but not T(H) 1 cytokines were spontaneously produced in DC-CD4(+) T cell co-cultures from children with FA and were not significantly increased after stimulation with milk extract, suggesting an ongoing activation in vivo. This hypothesis was further supported by evidence for elevated IL-5 and IL-13 protein in the plasma of children with both FA and EE. The only significant DC phenotypic differences were: (1) reduced levels of CD80 in EE subjects and (2) FcɛRI expression that correlated with serum IgE levels in both groups of subjects. This study suggests that DCs from children with FA and EE produce more pro-inflammatory cytokines, and that their CD4(+) T cells are spontaneously activated to produce T(H) 2 cytokines in the presence of FcɛRI-bearing DCs.

The mRNA expression of pro- and anti-inflammatory cytokines in T regulatory cells in children with type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune-mediated destruction of insulin-producing beta cells in the pancreas. T regulatory cells (Tregs) represent an active mechanism of suppressing autoreactive T cells that escape central tolerance. The aim of our study was to test the hypothesis that T regulatory cells express pro- and anti-inflammatory cytokines, elements of cytotoxicity and OX40/4-1BB molecules. The examined group consisted of 50 children with T1DM. Fifty two healthy individuals (control group) were enrolled into the study. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD3, anti-CD4, anti-CD25, anti-CD127, anti-CD134 and anti-CD137. Concurrently with the flow cytometric assessment of Tregs we separated CD4+CD25+CD127dim/- cells for further mRNA analysis. mRNA levels for transcription factor FoxP3, pro- and anti-inflammatory cytokines (interferon gamma, interleukin-2, interleukin-4, interleukin-10, transforming growth factor beta1 and tumor necrosis factor alpha), activatory molecules (OX40, 4-1BB) and elements of cytotoxicity (granzyme B, perforin 1) were determined by real-time PCR technique. We found no alterations in the frequency of CD4+CD25highCD127low cells between diabetic and control children. Treg cells expressed mRNA for pro- and anti-inflammatory cytokines. Lower OX40 and higher 4-1BB mRNA but not protein levels in Treg cells in diabetic patients compared to the healthy children were noted. Our observations confirm the presence of mRNA for pro- and anti-inflammatory cytokines in CD4+CD25+CD127dim/- cells in the peripheral blood of children with T1DM. Further studies with the goal of developing new strategies to potentiate Treg function in autoimmune diseases are warranted.

Sox2 Transduction Enhances Cardiovascular Repair Capacity of Blood-Derived Mesoangioblasts

Complementation of pluripotency genes may improve adult stem cell functions. Here we show that clonally expandable, telomerase expressing progenitor cells can be isolated from peripheral blood of children. The surface marker profile of the clonally expanded cells is distinct from hematopoietic or mesenchymal stromal cells, and resembles that of embryonic multipotent mesoangioblasts. Cell numbers and proliferative capacity correlated with donor age. Isolated circulating mesoangioblasts (cMABs) express the pluripotency markers Klf4, c-Myc, as well as low levels of Oct3/4, but lack Sox2. Therefore, we tested whether overexpression of Sox2 enhances pluripotency and facilitates differentiation of cMABs in cardiovascular lineages. Lentiviral transduction of Sox2 (Sox-MABs) enhanced the capacity of cMABs to differentiate into endothelial cells and cardiomyocytes in vitro. Furthermore, the number of smooth muscle actin positive cells was higher in Sox-MABs. In addition, pluripotency of Sox-MABs was shown by demonstrating the generation of endodermal and ectodermal progenies. To test whether Sox-MABs may exhibit improved therapeutic potential, we injected Sox-MABs into nude mice after acute myocardial infarction. Four weeks after cell therapy with Sox-MABs, cardiac function was significantly improved compared to mice treated with control cMABs. Furthermore, cell therapy with Sox-MABs resulted in increased number of differentiated cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. The complementation of Sox2 in Oct3/4-, Klf4-, and c-Myc-expressing cMABs enhanced the differentiation into all 3 cardiovascular lineages and improved the functional recovery after acute myocardial infarction.

Distinct Abnormalities in the Innate Immune System of Children with Down Syndrome

To analyze the frequency and phenotype of cells of the innate immune system in the peripheral blood of children with Down syndrome (DS). Flow cytometric analysis of expression of cell surface markers was performed in children with DS (n = 41) and healthy age-matched controls (n = 41). Compared with controls, children with DS had significantly lower absolute total leukocyte counts, lymphocytes, monocytes, and granulocytes, but 1.5-times higher absolute numbers of CD14(dim)CD16(+) monocytes (147 x 10(6)/L vs 93 x 10(6)/L; P = .02). This difference is fully explained by a higher percentage of CD14(dim)CD16(+) monocytes within the monocyte compartment (28.7% vs 13.4%; P <.001). The absolute numbers of myeloid dendritic cells were lower in DS (13.8 x 10(6)/L vs 22.7 x 10(6)/L; P <.001). The numbers of plasmacytoid dendritic cells and natural killer cells were normal. Absolute numbers of invariant natural killer T cells were very low overall, but significantly lower in children with DS than in controls (1.2 x 10(6)/L vs 3.7 x 10(6)/L; P = .01). Children with DS exhibited distinct abnormalities in cells of the innate immune system. Most strikingly, they had a high number of proinflammatory CD14(dim)CD16(+) monocytes. This elevated level of CD14(dim)CD16(+) monocytes may play an important role in the onset and maintenance of chronic inflammatory disease in DS.

Disturbances in some Gene Expression in T Regulatory Cells Separated from Children with Metabolic Syndrome

The metabolic syndrome (MS) is defined as a cluster of risk factors, including abdominal obesity, dyslipidaemia, glucose intolerance and hypertension, which increase the risk for coronary heart disease. The immunological aspects of obesity and MS, including the role of T regulatory cells, have been intensively investigated. The aim of this study was to determine whether there is any disturbance in T regulatory cells number and/or function in children with MS. The percentages of T regulatory cells in the peripheral blood of children fulfilling the International Diabetes Federation criteria of the disease (n = 47) were assessed. Treg cells were also separated for further analysis of multiple genes important in their function with the use of real-time RT-PCR. We did not observe any difference in Treg percentages between study and control group but there was lower expression of some molecules including transforming growth factor-beta and interleukin-12 family members in Treg cells separated from children with MS compared to the healthy subjects. Our study is the first to report significant disturbances in some gene expression in T regulatory cells separated from children with MS. The results should be useful for further research in this field, including immunotherapeutic interventions.

Zeta chain expression in T and NK cells in peripheral blood of children with nephrotic syndrome

The idiopathic nephrotic syndrome (INS) has been related to cellular immune disturbances. The zeta (zeta) chain, a component of the T-cell receptor/CD3 (TCR) complex and CD16 heterodimer in NK cells, plays a crucial role in T and NK cell activation and proliferation. The aim of our study was to examine zeta chain expression in CD4+, CD8+ T lymphocytes and NK cells in the peripheral blood of children with INS and to evaluate the effect of anti-CD3+rIL-2 stimulation on the level of zeta chain expression in the INS pediatric population. The study group consisted of 15 children with INS in relapse, 16 patients with INS in clinical remission, and 17 controls. The percentage of zeta-positive cells and the values of mean fluorescence intensity (MFI) were determined by flow cytometry. Compared with that in the controls, the percentage of zeta+ freshly isolated NK cells in children with INS in relapse was significantly lower, whereas, in CD3+/CD4+ and CD3+/CD8+ populations, no alteration was observed. There were no differences in the MFI values between the populations of freshly isolated cells either. Stimulation with anti-CD3+rIL-2 decreased the percentage of zeta+/CD4+ T cells and NKzeta+ cells in a significant way in all the groups analysed, whereas the percentage of zeta+/CD8+ T cells decreased significantly only in patients with INS in relapse. The altered pattern of zeta expression in fresh NK cells from children with INS in relapse, and the disturbed response of zeta+/CD8+ T cells to anti-CD3+rIL-2 stimulation in relapse, suggests the possible role of this chain in immune dysregulation in INS, particularly with regard to cytotoxic cells.

Comparison of Outcomes Between Transplantation From Unrelated Donor Umbilical Cord Blood and From Unrelated Donor Bone Marrow or Peripheral Blood in Children with Acute Leukemia.

Abstract 4340 IntroductionAlthough umbilical cord blood (UCB) is an accepted alternative to bone marrow or peripheral blood (BM/PB) for transplantation, allele-matched marrow or peripheral blood is generally regarded as the preferred graft source. Our aim is to compare leukemia-free survival after transplantation of unrelated donor UCB and allele-matched BM/PB, and to provide guidelines for selection of an appropriate donor and graft source in children with acute leukemia. Patients and MethodsOutcomes of 22 children with acute leukemia and transplanted with single unit UCB were compared with outcomes of 34 BM/PB recipients. All transplantations were performed in Samsung Medical Center between May 2003 and June 2009. Recipients of UCB were transplanted with grafts that were HLA-matched (n = 3) or HLA-mismatched for one (n = 15) or two antigens (n = 4). BM/PB recipients were transplanted with grafts that were HLA-matched (n = 20) or mismatched (n = 14). While allele-level typing for HLA-A, HLA-B, HLA-DRB1 and antigen-level typing for HLA-C was used for BM/PB transplantation, antigen level typing for HLA-A, HLA-B and HLA-DRB1 was used for UCB transplantation. Myeloablative conditioning regimens were used for both BM/PB and UCB transplantation. ResultsThe median times to neutrophil and platelet recovery were 15 (range 10–21) and 22 (12–29) days after BM/PB transplantation, and 17 (13–44) and 34 (24–148) days after UCB transplantation, respectively. The 4-year probabilities of leukemia-free survival were 58.0% after HLA-matched BM/PB transplants, 65.9% after HLA-mismatched BM/PB transplants, 66.7% after HLA-matched UCB transplants, 67.5% after one-mismatched UCB transplants with high cell dose (NC > 3.0 × 107/kg), 40.0% after one-mismatched UCB transplants with low cell dose (NC < 3.0 × 107/kg), and 33.3% after two-mismatched UCB transplants. The incidence of grade 3-4 acute graft-versus-host disease (GVHD) were 12.1% after BM/PB transplantation and 5.3% after UCB transplantation, respectively (P = 0.64). Rates of extensive chronic GVHD were 53.8% after BM/PB transplantation and 23.1% after UCB transplantation, respectively (P = 0.09). Transplant-related mortality rates were higher after UCB transplantation (21.7%) than BM/PB transplantation (2.9%) (P = 0.03). Relapse rates were similar after BM/PB transplantation (29.4%) and UCB transplantation (21.7%) (P = 0.56). ConclusionThese results support the use of HLA-matched or one-antigen HLA mismatched UCB in children with acute leukemia who need transplantation. Faster identification of a suitable cord blood unit may result in a timely transplantation avoiding delay that could expose the patient to the risk of losing the eligibility for transplant due to relapse or other complications. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Th17 Transcription Factor RORC2 Is Inversely Correlated with FOXP3 Expression in the Joints of Children with Juvenile Idiopathic Arthritis

To investigate the relationship between interleukin 17 (IL-17) producing T cells (Th17) and CD4+CD25+FOXP3+ regulatory T cells (Tregs) in blood and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA). Sixty-five children with JIA (18 males and 47 females, median age 6.2 yrs; 45 with oligoarticular and 20 with polyarticular course) and 75 age- and sex-matched healthy controls were studied. Flow cytometry was used to analyze the forkhead box P3 (FOXP3)-positive Treg cells in peripheral blood (PB) and synovial fluid mononuclear cells (SFMC). FOXP3 and retinoic-acid related orphan receptor C isoform 2 (RORC2) messenger RNA (mRNA) were assessed by real-time polymerase chain reaction analysis. Cytokines (IL-17 and Th1/Th2 related cytokines) were measured in culture supernatants of 11 paired PBMC and SFMC activated with PMA and ionomycin. FOXP3+ T cells and FOXP3 mRNA amounts were significantly lower in PB of children with JIA as compared with controls (p = 0.0002 and p = 0.001, respectively) and a higher percentage of Treg cells with concomitant higher level of FOXP3 transcript levels were observed in SF when compared with their PB counterparts (both p < 0.0001). SF CD4+FOXP3+ T cells were characterized by higher amounts of FOXP3 protein per cell when compared with peripheral CD4+FOXP3+ T cells, as revealed by the difference in FOXP3 median fluorescence intensity (median +/- SD, arbitrary units, 54 +/- 22.6 vs 19.5 +/- 4.2; p < 0.001). RORC2 transcript levels were higher in JIA joints when compared with matched PB samples (median fold increase 3.9, p < 0.0001) but negatively correlated with FOXP3 mRNA levels (r = -0.623, p = 0.04). Stimulated SFMC displayed an impaired ability to produce IL-17 when compared with PBMC and, interestingly, an inverse relationship between IL-17 levels and the percentage of CD4+CD25+FOXP3+ SF T cells (r = -0.510, p = 0.047) was seen. We demonstrated for the first time an increased synovial expression of the transcription factor of Th17, RORC2, in JIA, and its inverse relationship with FOXP3 mRNA. These results extend research on "Th17" and Tregs in JIA.

The B-cell Compartment in the Peripheral Blood of Children With Different Types of Primary Humoral Immunodeficiency

The aim of this study was to evaluate the B-cell compartment in the peripheral blood of children with different types of hypogammaglobulinemia: common variable immunodeficiency (CVID), transient hypogammaglobulinemia of infancy (THI), and selective IgA deficiency (SIgAD). We analyzed by flow cytometry the changes in the B-cell subsets with age and showed that children with an early-onset CVID develop similar pattern of B-cell subsets as adult patients with CVID with age, as the levels of memory B cells (CD19/CD27) and class-switched memory B cells (CD19/CD27/IgD/IgM), in contrast to age-matched control group, did not increase with age. Children with SIgAD displayed similar changes as patients with CVID only within the class-switched memory B-cell subpopulation. No significant differences in the level of memory B cells and class-switched memory B cells in children with THI in comparison to age-matched control group were observed. There were no differences in the percentage of immature B cells (CD19/CD21) among all studied groups. As B-cell subsets in children with THI were normal during entire period of hypogammaglobulinemia, the persistence of low levels of memory B-cell subsets in some children may facilitate the diagnosis of CVID.

Increases In CD25 + T Cell Numbers In Peripheral Blood Of Children With Allergic Asthma Correlate With Measures Of Airway Obstruction, But Not Serum IgE Levels

Increases In CD25 + T Cell Numbers In Peripheral Blood Of Children With Allergic Asthma Correlate With Measures Of Airway Obstruction, But Not Serum IgE Levels

Altered P-selectin and CD44 expression in the renal tissues and peripheral blood of children with IgA nephropathy

To understand the role of P-selectin (CD62P) and CD44 in mediating immune inflammation in the nephrotic process of children with IgA nephropathy (IgAN), cooperative expression of CD62P and CD44 in peripheral blood and renal tissues of IgAN children was investigated and its association with changes of histopathologic, serologic, and urinary properties was tested. Forty-six IgAN children were divided into three groups according to pathologic grades and clinical features. Fifteen blood samples from normal children and four normal renal biopsy specimens were used as controls. Plasma level of CD62P was detected by double antibody sandwich immunoradiometric assay; ELISA was used to determine serum level of CD44. Expression of CD62P and CD44 in renal tissues was determined by immunohistochemistry. Cooperative expression of CD62P and CD44 was detected in renal tissues and peripheral blood of IgAN children. Altered expression of CD62P and CD44 in peripheral blood significantly correlated not only with hematuria, proteinuria, serum cholesterol, and albumin, and with urine NAG and beta(2)-MG, but also with degree of tubulointerstitial injury in IgAN children. The evidence supported CD62P and CD44 as initial and promoting factors mediating immune inflammation in the nephrotic process in IgAN children. The cooperative expression profiles of CD62P and CD44 in renal tissues and peripheral blood combined with serologic and urinary predictors may be important in diagnosis of progression in children with IgAN.

Genomic analysis suggests higher susceptibility of children to air pollution

Differences in biological responses to exposure to hazardous airborne substances between children and adults have been reported, suggesting children to be more susceptible. Aim of this study was to improve our understanding of differences in susceptibility in cancer risk associated with air pollution by comparing genome-wide gene expression profiles in peripheral blood of children and their parents. Gene expression analysis was performed in blood from children and parents living in two different regions in the Czech Republic with different levels of air pollution. Data were analyzed by two different approaches: one method first selected significantly differentially expressed genes and analyzed these gene lists for overrepresented biological processes, whereas the other applied the T-profiler tool to directly perform pathway analyses on the total gene set without preselection of significantly modulated gene expressions. In addition, gene expressions in both children and adults were investigated for associations with micronuclei frequencies. Both analysis approaches returned considerably more genes or gene groups and pathways that significantly differed between children from both regions than between parents. Very little overlap was observed between children and adults. The two most important biological processes or molecular functions significantly modulated in children, but not in adults, are nucleosome and immune response related. Our study suggests differences between children and adults in relation to air pollution exposure at the transcriptome level. The findings underline the necessity of implementing environmental health policy measures specifically for protecting children's health.

Reduced Intracellular T-Helper 1 Interferon-Gamma in Blood of Newly Diagnosed Children With Crohn's Disease and Age-Related Changes in Th1/Th2 Cytokine Profiles

Abnormal cytokine production by T-helper 1 (Th1)/T-helper 2 (Th2) lymphocytes has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Few studies have examined Th1/Th2 cytokine status in pediatric IBD patients, and results have been inconsistent. We used flow cytometric detection of intracellular IFN-gamma/IL-4 cytokine production to investigate CD4+, Th1, and Th2 cells in the peripheral blood of children with untreated, newly diagnosed Crohn's disease (CD) (n = 23) and matched healthy controls (n = 49). Th1 cytokine levels were lower in CD patients compared with controls (p = 0.006) and strongly correlated with levels of albumin and hematocrit (r = 0.51, p = 0.007 and r = 0.35, p = 0.052, respectively). An age-dependent increase in Th1 cells was observed (p < 0.0005); however, no correlation was found between age, clinical end points, %CD4+, or Th2 cell numbers. In conclusion, the Th1 cytokine levels in blood are lower in early onset CD patients than in healthy children and are directly associated with disease-related clinical parameters. In future studies of pediatric IBD patients, it will be critical to consider the effect of age and disease progression on cytokine status in intestinal mucosa and peripheral blood.

Fetaler juveniler Granulosazelltumor mit Hermaphroditismus verus – pränatale Diagnostik, Management und postnatales Outcome

Fetal ovarian cysts are common during pregnancy and after delivery. Most of these cysts are simple cysts that involute during pregnancy or in the first months of life. However, complicated cyst with a heterogeneous structure and also possible and can result in various complications: rupture, hemorrhage, ascites, edema of the labia, compression of other viscera, and ovarian torsion. In this case report we describe rare diagnosis of a complicated fetal ovarian cyst with edema of the labia and moderate ascites. The neonate had ambiguous genitalia with clitoromegaly. The newborn underwent surgery with oophorectomy. During the operation a uterus with fallopian tubes was found. The pathological findings showed a juvenile granulosa cell tumor FIGO Ia. Karyotyping revealed a mosaic of 45, X/ 46, X mar (Y) in the peripheral blood as well as in the granulosa cell tumor. Because of a right side inguinal hernia, the child underwent a second surgery. Specimen taken from the abdominal gonad and the inguinal region showed testicular and dysplastic ovarian tissue. There were elevated levels of androgens in the child's peripheral blood due to the granulosa cell tumor. In summary, this case report describes a fetus with true hermaphroditism and a juvenile granulosa cell tumor diagnosed as a complicated ovarian cyst in the 32 (nd )week of pregnancy.